Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression.

The molecular mechanism by which roquin controls the expression of inducible costimulator (ICOS) to prevent autoimmunity remains unsolved. Here we show that in helper T cells, roquin localized to processing (P) bodies and downregulated ICOS expression. The repression was dependent on the RNA helicase Rck, and roquin interacted with Rck and the enhancer of decapping Edc4, which act together in mRNA decapping. Sequences in roquin that confer P-body localization were essential for roquin-mediated ICOS repression. However, this process did not require microRNAs or the RNA-induced silencing complex (RISC). Instead, roquin bound ICOS mRNA directly, showing an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region (3' UTR). Our results support a model in which roquin controls ICOS expression through binding to the 3' UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.

[Effects of berberine on DNFB-induced delayed type hypersensitivity in mice].

AIM: To investigate the effect of berberine (Ber) on DNFB-induced delayed type hypersensitivity (DTH) and explore the mechanism of the immunosuppression effect of berberine. METHODS: BALB/c mice were divided into three groups: control group, DTH group, and Ber-treated DTH group. The DTH group was sensitized to DNFB by painting the shaved abdomen with DNFB dissolved in propanone/olive oil. The Ber-treated DTH group was injected (i.p.) with berberine daily for 7 consecutive days, with the total dose of 30 mg/kg. The control group was treated with the solvent without DNFB. All mice were then challenged by painting 10 microL of 2 g/L DNFB on the left ears. The weight of right and left ears was measured at 48 h after challenge. Histological changes of mouse auricles were observed under light microscopy. Violet crystal staining was used to determine the effect of Ber on adhesion of mouse splenic lymphocytes to extracellular matrix (ECM). Annexin-V staining was used to detect the apoptotic rate of the lymphocytes in the lymph nodes. RESULTS: The results of ear weighting showed that Ber significantly inhibited DTH reaction (P<0.05). Histological observation indicated Ber reduced markedly the infiltration of lymphocytes. The adhesion of T lymphocytes to ECM was also notably decreased by Ber treatment (P<0.05). There was no obvious difference in apoptotic rates of the lymphocytes among Ber-treated DTH group, DTH group and control group (P>0.05). CONCLUSION: Ber can significantly inhibit the DNFB-induced DTH in mice. The reduced adhesion between mouse T lymphocytes and ECM may be one of the mechanisms of suppression of DTH by Ber.

One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation.

One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation.